Supercoiled Minivector DNA resists shear forces associated with gene therapy delivery
DJ Catanese, JM Fogg, DE Schrock, BE Gilbert… - Gene therapy, 2012 - nature.com
DJ Catanese, JM Fogg, DE Schrock, BE Gilbert, L Zechiedrich
Gene therapy, 2012•nature.comSupercoiled DNAs varying from 281 to 5302 bp were subjected to shear forces generated by
aerosolization or sonication. DNA shearing strongly correlated with length. Typical sized
plasmids (⩾ 3000 bp) degraded rapidly. DNAs 2000–3000 bp persisted∼ 10 min. Even in
the absence of condensing agents, supercoiled DNA< 1200 bp survived nebulization, and
increased forces of sonication were necessary to shear it. Circular vectors were
considerably more resistant to shearing than linear vectors of the same length. DNA …
aerosolization or sonication. DNA shearing strongly correlated with length. Typical sized
plasmids (⩾ 3000 bp) degraded rapidly. DNAs 2000–3000 bp persisted∼ 10 min. Even in
the absence of condensing agents, supercoiled DNA< 1200 bp survived nebulization, and
increased forces of sonication were necessary to shear it. Circular vectors were
considerably more resistant to shearing than linear vectors of the same length. DNA …
Abstract
Supercoiled DNAs varying from 281 to 5302 bp were subjected to shear forces generated by aerosolization or sonication. DNA shearing strongly correlated with length. Typical sized plasmids (⩾ 3000 bp) degraded rapidly. DNAs 2000–3000 bp persisted∼ 10 min. Even in the absence of condensing agents, supercoiled DNA< 1200 bp survived nebulization, and increased forces of sonication were necessary to shear it. Circular vectors were considerably more resistant to shearing than linear vectors of the same length. DNA supercoiling afforded additional protection. These results show the potential of shear-resistant Minivector DNAs to overcome one of the major challenges associated with gene therapy delivery.
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